BridgeBio has published results from its pivotal Phase 3 Propel 3 trial of oral infigratinib in children with achondroplasia in The New England Journal of Medicine, alongside new data showing statistically significant improvements in arm span presented at the International Congress of Children’s Bone Health (ICCBH).

The publication marks the first Phase 3 achondroplasia clinical trial to appear in the journal and builds on previously reported positive Phase 3 results for the investigational oral FGFR3 inhibitor.

The global Propel 3 study evaluated oral infigratinib in children with achondroplasia, the most common cause of disproportionate short stature. Achondroplasia is caused by an activating variant in the FGFR3 gene and is associated with a range of medical complications, including obstructive sleep apnoea, spinal stenosis, middle ear dysfunction and skeletal abnormalities.

According to the published data, Propel 3 met its primary endpoint, demonstrating a statistically significant improvement in annualised height velocity compared with placebo. The least squares mean treatment difference was 1.74 cm per year (p<0.0001), while the observed mean difference reached 2.10 cm per year.

The study also met its key secondary endpoint of improvement in height Z-score after 52 weeks, with a statistically significant increase compared with placebo (p<0.0001).

In a pre-specified exploratory analysis, oral infigratinib demonstrated a statistically significant improvement in body proportionality compared with placebo among children younger than eight years, representing more than half of participants enrolled in the study.

Additional data presented during a late-breaking oral presentation at ICCBH showed children receiving oral infigratinib achieved a statistically significant improvement in arm span compared with placebo. The least squares mean improvement of 0.37 standard deviations (p<0.0001) is the first placebo-controlled arm span improvement reported in an achondroplasia clinical trial after 52 weeks, according to BridgeBio.

The therapy was generally well tolerated throughout the study. Researchers reported no treatment-related serious adverse events, no discontinuations related to study treatment and three mild, transient cases of hyperphosphataemia that resolved without dose reductions or treatment discontinuation. No adverse events associated with FGFR1 or FGFR2 inhibition were reported.

Dr Ravi Savarirayan, global lead investigator for Propel 3, said: “The publication of our pivotal trial data (PROPEL 3) in the New England Journal of Medicine is a defining milestone for the field of skeletal dysplasia that reflects the years of rigorous clinical investigation from investigators and dedication from children and their families to make this breakthrough science possible.”

He added: “Presenting these late-breaking data at ICCBH reflects the significance of having an orally administered, mechanistically distinct treatment option that addresses achondroplasia and hypochondroplasia at their very source.”

BridgeBio also presented findings from observational research examining health-related quality of life in children with achondroplasia, which showed reduced quality of life across multiple patient-reported measures, particularly physical functioning. Separate qualitative research supported the use of patient-reported outcome measures in children with hypochondroplasia and their families.

The company plans to submit a New Drug Application to FDA during the third quarter of 2026 and a Marketing Authorisation Application to EMA in the second half of the year. If approved, oral infigratinib could become the first approved oral therapy for children with achondroplasia.

Oral infigratinib has previously received Breakthrough Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations from FDA for achondroplasia. The company is also continuing clinical development in hypochondroplasia and other skeletal dysplasia conditions.